[18F]SMBT-1

[18F]SMBT-1 is a novel radiotracer developed for positron emission tomography (PET) imaging of monoamine oxidase-B (MAO-B), which serves as a marker for reactive astrogliosis in the brain. This condition is associated with neurodegenerative diseases, particularly Alzheimer's disease[1][6]. The full chemical name of [18F]SMBT-1 is (S)-(2-methylpyrid-5-yl)-6-[(3-18F-fluoro-2-hydroxy)propoxy]quinoline[1][4]. It was developed through lead optimization from the first-generation tau PET tracer 18F-THK-5351[1]. In preclinical studies, [18F]SMBT-1 demonstrated excellent blood-brain barrier permeability, high brain uptake, rapid washout, and no radiolabeled metabolites in the brain of normal mice[1][8]. It shows high binding affinity to MAO-B (dissociation constant of 3.7 nM) while having low binding affinity to MAO-A and protein aggregates such as amyloid-β and tau fibrils[1][3]. The S-enantiomer of [18F]SMBT-1 has been found to have more favorable binding affinity and selectivity for MAO-B compared to the R-enantiomer, as well as better pharmacological and metabolic properties[4]. Clinical studies have shown that [18F]SMBT-1 binding is significantly higher in amyloid-positive Alzheimer's disease patients and, importantly, in amyloid-positive cognitively normal individuals compared to amyloid-negative controls[6]. This suggests that increased [18F]SMBT-1 binding is detectable at the preclinical stages of amyloid accumulation, potentially allowing for earlier detection of Alzheimer's disease pathology[6]. The radiotracer has been used in human studies to assess reactive astrogliosis across the Alzheimer's disease continuum, with results indicating that it could serve as a surrogate marker for this process[2][6].

Other names

(S)-(2-methylpyrid-5-yl)-6-[(3-18F-fluoro-2-hydroxy)propoxy]quinoline